The C–C Bond Activation Of Michael Addition Receptor Catalyzed By Rhodium Complex

The site and chemically selective C–C bond cleavage/activation and functionalization has been one of the most challenging targets.?-C cleavage of intermediates containing transition metal provides a potential useful method for the carbon-carbon bond activation.However,there is still lack of successful example for constructing functional group-rich product from com-mon synthetic building blocks with this strategy,due to the competitive side reactions,such as quenching of the transition metal intermediate by protic sources prior to the ?-C cleavage.Here we report the C–C bond cleavage/coupling of 2-(azetidin-3-ylidene)ac-etates with aryl boronic acids catalyzed by rhodium complex,producing the unsaturated ?-aminobutyric acid(GABA)derivates with moderate to excellent yields,with “conjugate addition / ?-C cleavage / protonation” strategy.This path is subtly controlled mainly by ligand effect,as well as functional groups on substrate,solvent effect and selection of proton source.We show how ?-C cleavage could occur under the competitive well-known protonation circumstances,even in water.A broad range of organoboronic acids,including that derived from Ezetimibe,react effectively with 2-(azetidin-3-ylidene)acetates and their analogs.The controls related to the selectivity are explicated using experimental study.The main research contents of this thesis are as follows:1.The rhodium-catalyzed reaction of tert-butyl 3-(2-methoxy-2-oxyethylene)azetidine-1-carboxylic acid and phenylboronic acid was selected as the template reaction to optimize the ligand,solvent and base,etc.Finally,trifluoromethyl-modified dppp was selected as the ligand,cyclopentyl methyl ether was used as the solvent,sodium tert-butoxide was used as the base,and tert-amyl alcohol was used as the protonation reagent.The target product was then obtained in high yield.2.The substrate scope of the reaction was investigated under the optimal reaction conditions,with variation of the aryl group of arylboronic acids,as well as a series of 2-(azetidin-3-alkylene)acetates and their analogs.The target products were obtained in moderate or good yields in these cases.The organic boric acid derived from Ezetimibe could be also successfully used in this reaction.3.The product was transformed with several reactions,including hydrolysis of ester groups,asymmetric hydrogenation of the double bond and lactamization,etc.4.A plausible catalytic cycle was proposed,after the experimental study on the mechanism.The experimental results were reasonably explicated.